83 research outputs found

    Nucleophilic Substitution Reaction of 1-Methoxy-6-nitroindole

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    Nucleophilic substitution reaction of 1-methoxy-6-nitro-indole

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    金沢大学大学院自然科学研究科生理活性物質科学金沢大学薬学部Nucleophilic substitution reaction of 1-methoxy-6-nitroindole (1) was examined. In the reaction with sodium methoxide or sodium cyanide as a nucleophile, 2- and 3-methoxy-6-nitroindoles, and 7-cyano-6-nitroindole were obtained, respectively. A novel methylene homologation at the 3-position was found in the reaction of 1 with sodium methyl sulfide or potassium salt of diethyl malonate to give 3-methylthiomethytyl-6-nitroindole and its 2-methylthio derivative, and diethyl 2-(6-nitroindol-3-yl)methylmalonate, respectively. Possible reaction mechanism is discussed

    GABA-A and GABA-B Receptors in Filial Imprinting Linked With Opening and Closing of the Sensitive Period in Domestic Chicks (Gallus gallus domesticus)

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    Filial imprinting of domestic chicks has a well-defined sensitive (critical) period lasting in the laboratory from hatching to day 3. It is a typical model to investigate the molecular mechanisms underlying memory formation in early learning. We recently found that thyroid hormone 3,5,3′-triiodothyronine (T3) is a determinant of the sensitive period. Rapid increases in cerebral T3 levels are induced by imprinting training, rendering chicks imprintable. Furthermore, the administration of exogenous T3 makes chicks imprintable on days 4 or 6 even after the sensitive period has ended. However, how T3 affects neural transmission to enable imprinting remains mostly unknown. In this study, we demonstrate opposing roles for gamma-aminobutyric acid (GABA)-A and GABA-B receptors in imprinting downstream of T3. Quantitative reverse transcription polymerase chain reaction and immunoblotting showed that the GABA-A receptor expression increases gradually from days 1 to 5, whereas the GABA-B receptor expression gradually decreases. We examined whether neurons in the intermediate medial mesopallium (IMM), the brain region responsible for imprinting, express both types of GABA receptors. Immunostaining showed that morphologically identified putative projection neurons express both GABA-A and GABA-B receptors, suggesting that those GABA receptors interact with each other in these cells to modulate the IMM outputs. The roles of GABA-A and GABA-B receptors were investigated using various agonists and antagonists. Our results show that GABA-B receptor antagonists suppressed imprinting on day 1, while its agonists made day 4 chicks imprintable without administration of exogenous T3. By contrast, GABA-A receptor agonists suppressed imprinting on day 1, while its antagonists induced imprintability on day 4 without exogenous T3. Furthermore, both GABA-A receptor agonists and GABA-B receptor antagonists suppressed T3-induced imprintability on day 4 after the sensitive period has ended. Our data from these pharmacological experiments indicate that GABA-B receptors facilitate imprinting downstream of T3 by initiating the sensitive period, while the GABA-A receptor contributes to the termination of the sensitive period. In conclusion, we propose that opposing roles of GABA-A and GABA-B receptors in the brain during development determine the induction and termination of the sensitive period

    Cross-enhancement of ANGPTL4 transcription by HIF1 alpha and PPAR beta/delta is the result of the conformational proximity of two response elements

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    BACKGROUND: Synergistic transcriptional activation by different stimuli has been reported along with a diverse array of mechanisms, but the full scope of these mechanisms has yet to be elucidated. RESULTS: We present a detailed investigation of hypoxia-inducible factor (HIF) 1 dependent gene expression in endothelial cells which suggests the importance of crosstalk between the peroxisome proliferator-activated receptor (PPAR) β/δ and HIF signaling axes. A migration assay shows a synergistic interaction between these two stimuli, and we identify angiopoietin-like 4 (ANGPTL4) as a common target gene by using a combination of microarray and ChIP-seq analysis. We profile changes of histone marks at enhancers under hypoxia, PPARβ/δ agonist and dual stimulations and these suggest that the spatial proximity of two response elements is the principal cause of the synergistic transcription induction. A newly developed quantitative chromosome conformation capture assay shows the quantitative change of the frequency of proximity of the two response elements. CONCLUSIONS: To the best of our knowledge, this is the first report that two different transcription factors cooperate in transcriptional regulation in a synergistic fashion through conformational change of their common target genes

    Penetration of the Optic Nerve or Chiasm by Anterior Communicating Artery Aneurysms: Three Case Reports

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    Although large and giant aneurysms can induce visual disturbance by compression of the anterior visual pathway, splitting and penetration of the optic apparatus are extremely rare. The authors describe three patients who underwent clipping surgery for anterior communicating artery aneurysm infiltrating into the optic nerve or chiasm. These findings were suspected on preoperative magnetic resonance imaging and confirmed at surgery. Two aneurysms were ruptured and one unruptured. The authors review the literature and discuss the mechanism of cranial nerve penetration by an aneurysm.ArticleNEURO-OPHTHALMOLOGY. 35(3):128-132 (2011)journal articl

    Experimental Study on Influence of Hardening of Isolator in Multiple Isolation Building

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    An innovative multiple isolation building system is proposed, and the influence of hardening in seismic isolators on the response of a multiple isolation building is investigated by shaking table vibration tests for a scaled structural model. From the observation in recent earthquake disasters in far-fault ground motions, e.g., the 2011 off the Pacific coast of Tohoku earthquake, a significant concern is reminded that the long-period and long-duration ground excitation may cause severe damages to the existing base-isolated buildings. In order to enhance the seismic vibration suppression performance of these buildings, the multiple isolation structure has been developed recently as one of the innovative solutions. The multiple isolation structure is defined as a seismic-isolated building, which has multiple isolation stories by inserting supplemental isolators in the middle story in addition to the base. In this paper, the advantages of the proposed multiple isolation system subjected to an extremely strong far-field earthquake ground motion as the worst scenario are studied by the vibration test for a scaled model. In the scaled model, a non-linear restoring-force characteristic (hardening) is provided by the geometrical non-linearity, which can be realized by inserting linear springs in the direction perpendicular to the vibration direction. The influence of this hardening property on the structural responses is studied by comparing with the responses of the same model without hardening effect. In the comparison with the base-isolated building, the fundamental seismic vibration suppression performances are evaluated in terms of the transfer functions of both a multiple isolation system and a base isolation system to the base input by sweeping frequencies of stationary sine waves using a controllable compact shaking table. In the numerical simulations, the effect of the friction in the isolation layers is also investigated

    NADH-O(2) oxidoreductase activity and mRNA expression of complex I (51 kDa, ND1) in postnatal intrinsic muscle of rat tongue

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    Complex I is one of the respiratory chain enzymes related to NADH dehydrogenase and is an encoded gene product derived from both nuclear and mitochondrial genomes. Transcription levels of ND1 (mitochondrial) and 51 kDa (nuclear) subunits of complex I in the postnatal development of the intrinsic muscle in rat tongues were determined by Northern blot analysis. Enzyme activity levels were determined by NADH staining with tetrazolum salt, and oxygen consumption of NADH-O(2) oxidoreductase activity using a Clark-type electrode. The detailed structure of the mitochondria was observed using electron microscopy. The cross-sectional area of the mitochondria gradually increased during postnatal development, and the cristae also became complex, despite the length of mitochondria in muscle fibre being constant. The mitochondria density increased from birth to 15 days of age, and declined slightly afterwards. This pattern of density resembled that of NADH-O(2) oxidoreductase activity. The level of mRNA for ND1 through Northern blot analysis gradually increased from birth to 15 days of age and was highest at 21 days. For 51 kDa, the level was highest at 0 days and fell thereafter to a constant low. This suggests that the production of NADH dehydrogenase is limited by 51 kDa of Complex I derived from nuclear genomes rather than by the increase in mitochondria and composition of muscle fibre types due to changes in feeding behaviour
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